Sensation Of Coolness Research Articles

Do products containing menthol exacerbate allergic rhinitis? A narrative review.

The aim of this paper is to review whether products containing menthol exacerbate allergic rhinitis. A literature survey was performed on PubMed, Google and Google Scholar concerning allergic rhinitis (AR). Allergic rhinitis is an inflammatory condition of the nasal mucosa characterized by wheeze, congestion, nasal pruritus and discharge, or any combination thereof. Menthol is a naturally occurring phytochemical, with the formula C10H20O. The L-isomeric form creates the typical odor of peppermints and causes a sensation of coolness when applied to the skin or mucosae. Inhaling menthol vapor is known to affect the respiratory system in a number of different ways. The cooling agent, menthol, is also recognized as a trigger for asthma, AR and urticaria. The menthol molecule stimulates the TRPM8 receptor and may stimulate histamine release in a dose-dependent manner from RBL-2H3 cell cultures. The addition of menthol to products produces symptomatic relief in some patients by providing an impression of freer nasal air flow. It does this by stimulating cold receptors on branches of the fifth cranial nerve. Menthol is capable of provoking allergic hypersensitivity reactions and disorders, including asthma, AR and urticaria. It may also trigger an anaphylactic response. The use of menthol-containing products is best avoided in cases where an allergic disorder exists.

Comparative evaluation of some comfort properties of denim fabrics including dual-core yarns containing wool and elastane yarn

The ability of being preferable in many styles has made denim fabric essential product of wardrobe. However, denim fabrics have disadvantages such as insufficient insulation, cooler sensations and liquid transfer restricting its use in cold weather due to its’ raw material and structure. In this study, dual-core weft yarn containing wool yarn as the first core and elastane filaments as the second core was used in denim production in order to improve the mentioned functional properties and provide better thermal comfort properties, especially during cold weather. The performances of fabric from dual-core weft yarns containing wool/elastane (WDC) have been examined comparatively with equivalent core-spun containing elastane (C) and dualcore weft yarns containing T400/elastane (T DC). It was concluded that fabrics with WDC weft yarns have lower thickness, water vapor permeability and higher elasticity, air permeability values when it was compared with other fabric types, which contain C and TDC weft yarns.

Popliteal Artery Entrapment Syndrome: A Diagnostic and Treatment Enigma for Orthopaedic Surgeons.

Popliteal artery entrapment syndrome (PAES) is an uncommon condition that causes recurrent posterior leg pain and foot paresthesia in running athletes. This condition occurs most commonly due to an accessory or abnormal implant of the medial head of the gastrocnemius muscle. It may mimic or coincide with other chronic conditions of the lower extremity including chronic exertional compartment syndrome but is most consistent with vascular claudication. Clinical features that distinguish PAES from other causes of leg pain include a sensation of coolness of the posterior leg during exercise and associated paresthesia of the plantar aspect of the foot. Physical examination often reveals decreased intensity of the posterior tibial or dorsalis pedis pulses with passive dorsiflexion or active plantarflexion of the ankle. Diagnostic tests that confirm the presence of PAES include lower extremity angiography during active resisted plantarflexion or maximal passive dorsiflexion, and magnetic resonance angiography done after exercise provocation. Nonsurgical treatment with physical therapy and stretching of the gastrocnemius complex should be done as the first line of treatment. When conservative treatments are ineffective, referral to a vascular specialist for surgical intervention with a muscular band excision or transection, vascular bypass, or arterial reconstruction is necessary.

The effect of body surface area exposure to menthol on temperature regulation and perception in men.

In warm conditions topical application of menthol increases cool sensations and influences deep body temperature. The purpose of this experiment was to explore whether different body surface areas (BSA) exposed to menthol influence these responses. It was hypothesized that the forcing function exerted by menthol will be proportionally related to BSA. Using a within-participant design, 13 participants underwent three BSA exposures (Small [S; finger]; Medium [M; arm]; Large [L; upper/lower body]) to 4.13% menthol, and one Placebo exposure. During each exposure participants rested supine in a tent (30°C, 50%rh) for 30-min before their intervention and 30-min thereafter. Measures included thermal sensation, thermal comfort, irritation, skin blood flow (finger SkBF; laser Doppler flowmetry), rectal temperature (Tre), and skin temperature (chest, forearm, thigh, calf). The Area Under the Curve from minute 30 to 60 was calculated and analyzed using a one-way ANOVA or Friedman's test with post-hoc testing (0.05 alpha level). There was no significant difference in any measure of thermometry (p>0.05), while SKBF was significantly lowered in L, M, and S vs. P respectively (p<0.05). Participants in L felt cooler vs. P and S (p<0.05). Losses in thermal comfort were noted in L and M vs. P and S (p<0.05), along with increased irritation in L vs. S (p<0.05). Despite similar skin temperatures, larger BSA's exposed to menthol caused cooler sensations, likely due to the activation of a larger pool of menthol-sensitive neurons. This occurred in the absence of thermal discomfort and without perceptions of irritation exceeding 'weak'. Larger BSA's also exhibited greater alterations in Tre, likely driven by a reduction in SkBF, but despite this mean body temperature was regulated suggesting the thermoregulatory system can cope with the range of BSA exposures studied herein.

Menthol Use for Performance in Hot Environments

Menthol is a compound of plant origin and has recently been used to aid exercise performance in hot, humid environments. Menthol creates a sensation of coolness when applied to the skin or mucosal surfaces stimulating the cold receptors. In these environments, fatigue is known to be accelerated and feelings of being hot are one of the main contributors to the early onset of fatigue. However, current research indicates that nonthermal perceptual cooling interventions could alter behavior in the heat by reducing thermal perception. This would allow the athlete to feel cooler when exercising at the same work rate in the heat. Menthol has been investigated as an internal and external intervention. Greater benefits have currently been found for internal interventions than external methods. Future research should focus on the mechanisms, dosage, and timing of both internal and external interventions, and the role menthol could play within speed or strength.

A study on the parameter ranges of the locally supplied air in a task ambient conditioning system with chest exposure

The benefits of task ambient conditioning in improving thermal comfort and indoor air quality have been demonstrated in recent studies. The potential use of task ambient conditioning for improving thermal comfort when the room air temperature is beyond the suggested range in mixing ventilation; however, has not been fully explored. A newly developed task ambient conditioning with chest exposure was, therefore, suggested at the room air temperature of 28°C (82.4°F), which is higher than the normally set temperature under cooling conditions in mixing ventilation. The present study aims to explore the appropriate air parameter ranges of the local airflow, but not to develop the practical system. Assessments of the thermal environment were performed by subjective questionnaires under nine distinct conditions with task ambient conditioning with chest exposure as well as the ambient environment in a climate chamber. The thermal sensations under the nine conditions with task ambient conditioning with chest exposure were nearly thermal neutral or slightly cool, while a slightly warm sensation was experienced in an ambient environment. Thermal sensation votes indicated cooler sensations with a decrease in the temperature of the locally supplied air, and with an increase in the velocity of locally supplied air, as well as in the vent diameter. The locally supplied airflow of task ambient conditioning with chest exposure obviously improved thermal comfort, the percentage of discomfort was reduced to 20% or less. Furthermore, the appropriate ranges of airflow parameters (air temperature, air velocity, and vent diameter) of task ambient conditioning with chest exposure were demonstrated, to aid the practical development of task ambient conditioning with chest exposure systems.

Knitted fabric properties influencing coolness to the touch and the relationship between subjective and objective coolness measurements

The aims of this study were to identify the optimal combination of knitted fabric properties that influence the sensation of coolness and to ascertain the relationship between subjective and objective coolness measurements. Test fabrics included eight cool-touch nylon knitted fabrics and four other knitted fabrics. The physical properties and surface characteristics of the fabrics were assessed. Coolness sensation was determined by the Thermolabo II instrument to provide an objective measurement, expressed as Qmax. A forearm test and palm-of-hand test were used as subjective measurements. Pore volume ratio and geometric roughness had a significant effect on coolness sensation expressed via Qmax. Stiffness and weight influenced the forearm test. Pore volume ratio and the coefficient of steel–fabric friction affected the coolness sensation measured by the palm-of-hand test. Nylon/spandex (78/22) tricot was the coolest of all samples, such that its characteristics were thought to represent the optimal combination of knitted fabric properties for a cooling fabric, that is, a high and balanced stitch density of 150 × 130, light in weight of 161.4 g/m2, a pore volume ratio of 69.4%, medium geometric roughness, and a thin pliable knitted fabric. The objective measurements were highly correlated with the palm-of-hand test, but not with the forearm test because only the palm-of-hand test had a test set-up that was similar to the objective test. Although the objective and forearm test set-ups were only slightly different, coolness assessed with the forearm test was not correlated with coolness assessed with objective measurements.

Evidence of viscerally-mediated cold-defence thermoeffector responses in man.

Visceral thermoreceptors that modify thermoregulatory responses are widely accepted in animal but not human thermoregulation models. Recently, we have provided evidence of viscerally-mediated sweating alterations in humans during exercise brought about by warm and cool fluid ingestion. In the present study, we characterize the modification of shivering and whole-body thermal sensation during cold stress following the administration of a graded thermal stimuli delivered to the stomach via fluid ingestion at 52, 37, 22 and 7°C. Despite no differences in core and skin temperature, fluid ingestion at 52°C rapidly decreased shivering and sensations of cold compared to 37°C, whereas fluid ingestion at 22 and 7°C led to equivalent increases in these responses. Warm and cold fluid ingestion independently modifies cold defence thermoeffector responses, supporting the presence of visceral thermoreceptors in humans. However, the cold-defence thermoeffector response patterns differed from previously identified hot-defence thermoeffectors. Sudomotor activity is modified by both warm and cold fluid ingestion during heat stress, independently of differences in core and skin temperatures, suggesting independent viscerally-mediated modification of thermoeffectors. The present study aimed to determine whether visceral thermoreceptors modify shivering responses to cold stress. Ten males (mean±SD: age 27±5years; height 1.73±0.06m, weight 78.4±10.7kg) underwent whole-body cooling via a water perfusion suit at 5°C, on four occasions, to induce a steady-state shivering response, at which point two aliquots of 1.5mlkg-1 (SML) and 3.0mlkg-1 (LRG), separated by 20min, of water at 7, 22, 37 or 52°C were ingested. Rectal, mean skin and mean body temperature (Tb ), electromyographic activity (EMG), metabolic rate (M) and whole-body thermal sensation on a visual analogue scale (WBTS) ranging from 0mm (very cold) to 200mm (very hot) were all measured throughout. Tb was not different between all fluid temperatures following SML fluid ingestion (7°C: 35.7±0.5°C; 22°C: 35.6±0.5°C; 37°C: 35.5±0.4°C; 52°C: 35.5±0.4°C; P=0.27) or LRG fluid ingestion (7°C: 35.3±0.6°C; 22°C: 35.3±0.5°C; 37°C: 35.2±0.5°C; 52°C: 35.3±0.5°C; P=0.99). With SML fluid ingestion, greater metabolic rates and cooler thermal sensations were observed with ingestion at 7°C (M: 179±55W, WBTS: 29±21mm) compared to 52°C (M: 164±34W, WBTS: 51±28mm; all P<0.05). With LRG ingestion, compared to shivering and thermal sensations with ingestion at 37°C (M: 215±47W, EMG: 3.9±2.5% MVC, WBTS: 33±2mm), values were different (all P<0.05) following ingestion at 7°C (M: 269±77W, EMG: 5.5±0.9% MVC, WBTS: 14±12mm), 22°C (M: 270±86W, EMG: 5.6±1.0% MVC, WBTS: 18±19mm) and 52°C (M: 179±34W, EMG: 3.3±2.1% MVC, WBTS: 53±28mm). In conclusion, fluid ingestion at 52°C decreased shivering and the sensation of coolness, whereas fluid ingestion at 22 and 7°C increased shivering and sensations of coolness to similar levels, independently of core and skin temperature.

Forearm test for disposable antibacterial foot sweat pads

Purpose – The purpose of this paper is to obtain thermal sensations arise during skin-antibacterial modified foot sweat pad contact by subjective forearm test carried out on 14 males. Design/methodology/approach – Sweat pads were designed for the foot and topsheet layers, constituting of polypropylene (PP) or polylactic acid (PLA) nonwoven fabrics, were modified by herbal antibacterial agents (cinnamaldehyde, geraniol, phenylethyl alcohol). Antibacterial agents were applied directly or within polymers which prepared by three different polymerization methods. Dry and wet pads (including water 50 percent of absorption capacity) were placed on the forearms of the subjects for a constant period under controlled environmental conditions. Liquid absorption and transfer characteristics of the topsheet layers were measured by standard methods (drop, absorption capacity, wetback tests) and moisture management tester parameters. Subjective coolness and dampness sensations arise during first touch of the pads were gathered and results were discussed according to liquid absorption and transfer characteristics of the sweat pads which differ according to topsheet fabrics and different antibacterial treatments. Findings – The paper showed that, direct or polymerization-based antibacterial applications created significantly different coolness and dampness sensations when compared with raw PP and PLA fabrics. Significant relationships were obtained between coolness sensation and both dampness sensation and absorption capacity results. Originality/value – Forearm test is normally applied on standard fabrics but in this study, it was applied on a disposable product which is used within foot clothing system.

The influence of a menthol and ethanol soaked garment on human temperature regulation and perception during exercise and rest in warm, humid conditions

This study assessed whether donning a garment saturated with menthol and ethanol (M/E) can improve evaporative cooling and thermal perceptions versus water (W) or nothing (CON) during low intensity exercise and rest in warm, humid conditions often encountered in recreational/occupational settings. It was hypothesised there would be no difference in rectal (Tre) and skin (Tsk) temperature, infra-red thermal imagery of the chest/back, thermal comfort (TC) and rating of perceived exertion (RPE) between M/E, W and CON, but participants would feel cooler in M/E versus W or CON. MethodsSix volunteers (mean [SD] 22 [4] years, 72.4 [7.4] kg and 173.6 [3.7] cm) completed (separate days) three, 60-min tests in 30°C, 70%rh, in a balanced order. After 15-min of seated rest participants donned a dry (CON) or 80mL soaked (M/E, W) long sleeve shirt appropriate to their intervention. They then undertook 30-min of low intensity stepping at a rate of 12steps/min on a 22.5cm box, followed by 15-min of seated rest. Measurements included heart rate (HR), Tre, Tsk (chest/back/forearm), thermal imaging (back/chest), thermal sensation (TS), TC and RPE. Data were reported every fifth minute as they changed from baseline and the area under the curves were compared by condition using one-way repeated measures ANOVA, with an alpha level of 0.05. ResultsTre differed by condition, with the largest heat storage response observed in M/E (p<0.05). Skin temperature at the chest/back/forearm, and thermal imaging of the chest all differed by condition, with the greatest rate of heat loss observed in W and M/E respectively (p<0.01). Thermal sensation differed by condition, with the coolest sensations observed in M/E (p<0.001). No other differences were observed. ConclusionsBoth M/E and W enhanced evaporative cooling compared CON, but M/E causes cooler sensations and a heat storage response, both of which are likely mediated by menthol.

Dynamic thermal imaging analysis in the effectiveness evaluation of warming and cooling formulations

Warming cosmetics and medicines are used to accelerate recovery from injuries whereas cooling preparations are used in the pains of muscles, joints, spine, bruises or edema. The paper verifies subjective heating or warming sensations with respect to the measured temperature changes. The influence of three formulations, labelled C1, C2, W1, on skin reaction was tested. The first two formulations (C1, C2) had a cooling effect while the formulation W1 had warming properties. Two hundred thermal images with a resolution of N×M=120×120pixel were acquired with the Flir i7 infrared camera. The paper also shows how to analyse low resolution thermal images and their practical usefulness. For this purpose, a dedicated algorithm for image analysis and processing, which uses morphological operations, segmentation and area analysis, was applied. Application of both C1 and C2 resulted in subjective perception of feeling cold. Approximately 7min following application of the formulation C1, the skin temperature returned to baseline levels. The minimum skin temperature after using the formulation C1 was 27.5°C and it was registered at the time of application. Application of W1, which by definition is a warming formulation, caused a sensation of coolness in the first minutes following the application. The perception of cool and warm sensations after the application of topical formulations is in no way correlated with the skin temperature assessed using a thermal imaging method.

여름철 실내 쾌적온도 설정 기준의 적합성

ABSTRACT This study was to provide the information for optimum utilization of the air-conditioning system in the human health and energy saving perspective. Subjects were 17 male and female college students(7 males and 10 females) with normal weight. They wore a short sleeved shirt, knee length trousers, socks, and underwear(0.4clo). They were asked to choose the preferred temperature from different environmental temperatures(28℃, 25℃). The physiological responses were measured and the subjective sensation was voted during the step changes of environmental temperature, starting at 28℃ to 25℃ with 1℃ decrease every 20 minutes. The preferred temperature was 25.9±0.4℃ for males and 26.9±0.2℃ for females at 28℃ and 24.8±0.6℃ for males and 25.6±0.1℃ for females at 25℃. The preferred temperature decreased about 1.3℃ while the environmental temperature changed 3℃. During the environmental step changes, mean skin temperature decreased more in females while the oxygen uptake and rectal temperature were kept constant for both males and females. We found the preferred temperature was affected by the exposed temperature and the thermal sensation in the condition. Subjects preferred a lower environmental temperature when they were exposed to a lower temperature with cooler sensation. Therefore, in the perspective of human health and energy saving, it is recommended to start setting the air-conditioning temperature higher than the preferred temperature. Key words: air-conditioning system, environmental step change, preferred temperature, summer indoor temperature

Effects of wind application on thermal perception and self-paced performance

Physiological and perceptual effects of wind cooling are often intertwined and have scarcely been studied in self-paced exercise. Therefore, we aimed to investigate (1) the independent perceptual effect of wind cooling and its impact on performance and (2) the responses to temporary wind cooling during self-paced exercise. Ten male subjects completed four trials involving 15 min standardized incremental intensity cycling, followed by a 15-km self-paced cycling time trial. Three trials were performed in different climates inducing equivalent thermal strain: hot humid with wind (WIND) and warm humid (HUMID) and hot dry (DRY) without wind. The fourth trial (W3-12) was equal to HUMID, except that wind cooling was unexpectedly provided during kilometers 3-12. Physiological, perceptual and performance parameters were measured. Subjects felt generally cooler during the WIND than the HUMID and DRY trials, despite similar heart rate, rectal and skin temperatures and a WBGT of ~4 °C higher. The cooler thermal sensation was not reflected in differences in thermal comfort or performance. Comparing W3-12 to HUMID, skin temperature was 1.47 ± 0.43 °C lower during the wind interval, leading to more favorable ratings of perceived exertion, thermal sensation and thermal comfort. Overall, power output was higher in the W3-12 than the HUMID-trial (256 ± 29 vs. 246 ± 22 W), leading to a 67 ± 48 s faster finish time. In conclusion, during self-paced exercise in the heat, wind provides immediate and constant benefits in physiological strain, thermal perception and performance. Independent of physiological changes, wind still provides a greater sensation of coolness, but does not impact thermal comfort or performance.

Don’t get burned by OTC topical analgesics

Some consumers have reported receiving serious skin injuries while using certain OTC topical pain relievers to relieve mild muscle and joint pain, FDA has warned. When these products are applied to the skin, they should produce a local sensation of warmth or coolness; they should not cause pain or skin damage. The reported cases of skin injuries ranged from first- to third-degree burns, often following one application of the product.

Effect of Warm-Up and Precooling on Pacing During a 15-km Cycling Time Trial in the Heat

The best way to apply precooling for endurance exercise in the heat is still unclear. The authors analyzed the effect of different preparation regimens on pacing during a 15-km cycling time trial in the heat. Ten male subjects completed four 15-km time trials (30°C), preceded by different preparation regimes: 10 min cycling (WARM-UP), 30 min scalp cooling of which 10 min was cycling (SC+WARM-UP), ice-slurry ingestion (ICE), and ice slurry ingestion + 30 min scalp cooling (SC+ICE). No differences were observed in finish time and mean power output, although power output was lower for WARM-UP than for SC+ICE during km 13-14 (17 ± 16 and 19 ± 14 W, respectively) and for ICE during km 13 (16 ± 16 W). Rectal temperature at the start of the time trial was lower for both ICE conditions (~36.7°C) than both WARMUP conditions (~37.1°C) and remained lower during the first part of the trial. Skin temperature and thermal sensation were lower at the start for SC+ICE. The preparation regimen providing the lowest body-heat content and sensation of coolness at the start (SC+ICE) was most beneficial for pacing during the latter stages of the time trial, although overall performance did not differ.

Direct inhibition of the cold-activated TRPM8 ion channel by Gαq

Activation of the TRPM8 ion channel in sensory nerve endings produces a sensation of pleasant coolness. Here we show that inflammatory mediators such as bradykinin and histamine inhibit TRPM8 in intact sensory nerves, but do not do so via conventional signalling pathways. The G-protein subunit Gaq instead binds to TRPM8 and when activated by a Gq-coupled receptor directly inhibits ion channel activity. Deletion of Gaq largely abolished inhibition of TRPM8, and inhibition was rescued by a Gaq chimera whose ability to activate downstream signalling pathways was completely ablated. Activated Gaq protein, but not Gβγ, potently inhibits TRPM8 in excised patches. We conclude that Gaq pre-forms a complex with TRPM8 and inhibits activation of TRPM8, following activation of G-protein coupled receptors, by a direct action. This signalling mechanism may underlie the abnormal cold sensation caused by inflammation.

Preparation of Water in Oil Type Cream with High Content of Water Containing &lt;i&gt;Kochia scoparia&lt;/i&gt; Fruit and &lt;i&gt;Cnidium monnieri&lt;/i&gt; Fruit

Kikisui is a herbal lotion containing Kochia scoparia Fruit and Cnidium monnieri Fruit that is clinically used as an antipruritic for itchy dry skin. However, this formulation is unsuitable for inducing a prolonged effect. Here, we attempted to change the formulation from a lotion to a cream. The cream we chose was a water-in-oil (W/O) type emulsion for enhancing skin compatibility. In addition, the high water content imparts a sensation of coolness. However, it is difficult to prepare a stable W/O type cream with high water content using a mechanical mixing method. Instead, we prepared the W/O type emulsion using liquid crystals. Water containing cocamidopropyl betaine was added to a dispersed phase comprising an oil phase of oleic acid and liquid paraffin that was constantly stirred. Addition of an aqueous solution containing Kochia scoparia Fruit and Cnidium monnieri Fruit decreased the stability of the cream. However, addition of glycerin as a humectant, and ethyl p-hydroxybenzoate/n-butyl p-hydroxybenzoate as preservatives enhanced the stability of the cream. The stability of the emulsion was correlated with the apparent viscosity of the cream. The final W/O type cream had a water content of 83% and was stable for more than 6 months at 4°C. Furthermore, ostol, which is one of the main biologically active herbal compounds, was also stable for more than 6 months.

Ocular dryness excites two classes of corneal afferent neurons implicated in basal tearing in rats: involvement of transient receptor potential channels

This study reports the findings of two classes of corneal afferents excited by drying of the cornea (dry responses) in isoflurane-anesthetized rats: cold-sensitive (CS; 87%) and cold-insensitive (CI; 13%) neurons. Compared with CI neurons, CS neurons showed significantly higher firing rates over warmer corneal temperatures (~31-15°C) and greater responses to menthol, drying, and wetting of the cornea but lower responses when hyperosmolar solutions were applied to the ocular surface. We proposed that the dry responses of these corneal afferents derive from cooling and an increased osmolarity of the ocular surface, leading to the production of basal tears. An ocular application of the transient receptor potential channel TRPM8 antagonist BCTC (20 μM) decreased the dry responses by ~45-80% but failed to completely block them, whereas the TRPA1 antagonist HC030031 did not influence the responses to drying of the cornea or hyperosmolar tears. Furthermore, the responses produced by cold stimulation of the cornea accounted for only 28% of the dry responses. These results support the view that the stimulus for basal tearing (corneal dryness) derives partly from cooling of the cornea that activates TRPM8 channels but that non-TRPM8 channels also contribute significantly to the dry responses and to basal tearing. Finally, we hypothesized that activation of TRPM8 by cooling in CS corneal afferents not only gives rise to the sensation of ocular coolness but also to the "wetness" perception (Thunberg's illusion), whereas a precise role of the CI afferents in basal tearing and other ocular dryness-related functions such as eye blink and the "dryness" sensation remain to be elucidated.

Comparison of beraprost and ticlopidine in Chinese patients with chronic peripheral arterial occlusion: a multicenter, single-blind, randomized, controlled study

Background: Chronic peripheral arterial occlusion (CPAO) is a progressive disease that is associated with a variety of symptoms, the 4 most common being a sensation of coolness in the limbs, intermittent claudication (in which pain occurs on walking), limb pain (which occurs spontaneously at rest), and ischemic leg ulcers. Beraprost sodium is an oral prostaglandin I 2 analogue that may ameliorate these symptoms. Objective: The aim of this study was to compare the efficacy and tolerability of beraprost sodium and ticlopidine hydrochloride in the treatment of patients with CPAO in China. Methods: In this multicenter, single-blind, controlled study, patients with CPAO were randomly assigned to receive beraprost 120-μg tablet TID or ticlopidine 500-mg tablet BID, both administered orally. The clinical efficacy of the drugs was assessed using the 4 main symptoms of CPAO. Ankle-brachial index (ABI) also was measured as a clinical pharmacologic procedure. Adverse events were assessed throughout the study. Results: A total of 124 patients (96 men, 28 women; mean [SD] age, 65 [12] years) were enrolled in 3 hospitals. Data from 119 patients (93 men, 26 women; mean [SD] age, 65 [12] years) were included in the efficacy analysis (64 and 55 patients in the beraprost and ticlopidine groups, respectively). Although all 4 symptoms of CPAO were ameliorated after 3 and 6 weeks of treatment with both drugs, only the cool sensation was significantly improved with beraprost compared with ticlopidine at 6 weeks ( P<0.05). ABI was significantly increased with both beraprost and ticlopidine at 6 weeks versus baseline ( P<0.001 and P<0.01, respectively), suggesting that this pharmacologic action may have led to their beneficial effect on various symptoms. The tolerability analysis included 123 patients (65 and 58 patients in the beraprost and ticlopidine groups, respectively). The numbers of patients who (1) experienced adverse events (AEs), (2) experienced adverse drug reactions, and (3) withdrew due to AEs were significantly smaller in the beraprost group than in the ticlopidine group ( P<0.001, P<0.05, and P<0.05, respectively). Conclusions: In this study population of patients with CPAO, beraprost ameliorated cool sensation in the limbs, intermittent claudication, limb pain, and ischemic/leg ulcers. Beraprost was more efficacious in relieving CPAO symptoms and was better tolerated than ticlopidine. Beraprost may be useful for the treatment of patients with CPAO, but more studies are needed.

An unusual case of clarithromycin associated ergotism

A 41-year-old woman presented to the Emergency Department complaining of a 4-day history of worsening lower leg pain, pallor, and a sensation of coolness aggravated by exertion. Evaluation revealed severe lower extremity vasospasm. She recently had been prescribed clarithromycin for “flu-like” symptoms, and for many years had been taking a caffeine-ergotamine preparation for migraine headaches. Clarithromycin is known to interfere with ergotamine metabolism. This drug interaction is often not recognized. Ergot alkaloids are commonly used for migraine headaches and have vasoconstrictive properties. In a patient with ergotamine toxicity, these vasoconstrictive properties can lead to frank ischemia. We reviewed the literature for reports of ergotamine-associated ischemia and for reports of ergotamine toxicity caused by drug-drug interaction.